Wolbachia are maternally transmitted intracellular bacteria that invade insect populations by manipulating their reproduction and immunity and thus limiting the spread of numerous human pathogens. ...Experimental Wolbachia infections can reduce Plasmodium numbers in Anopheles mosquitoes in the laboratory, however, natural Wolbachia infections in field anophelines have never been reported. Here we show evidence of Wolbachia infections in Anopheles gambiae in Burkina Faso, West Africa. Sequencing of the 16S rRNA gene identified Wolbachia sequences in both female and male germlines across two seasons, and determined that these sequences are vertically transmitted from mother to offspring. Whole-genome sequencing of positive samples suggests that the genetic material identified in An. gambiae belongs to a novel Wolbachia strain, related to but distinct from strains infecting other arthropods. The evidence of Wolbachia infections in natural Anopheles populations promotes further investigations on the possible use of natural Wolbachia-Anopheles associations to limit malaria transmission.
Human pathogens that are transmitted by insects are a global problem, particularly those vectored by mosquitoes; for example, malaria parasites transmitted by Anopheles species, and viruses such as ...dengue, Zika and chikungunya that are carried by Aedes mosquitoes. Over the past 15 years, the prevalence of malaria has been substantially reduced and virus outbreaks have been contained by controlling mosquito vectors using insecticide-based approaches. However, disease control is now threatened by alarming rates of insecticide resistance in insect populations, prompting the need to develop a new generation of specific strategies that can reduce vector-mediated transmission. Here, we review how increased knowledge in insect biology and insect-pathogen interactions is stimulating new concepts and tools for vector control. We focus on strategies that either interfere with the development of pathogens within their vectors or directly impact insect survival, including enhancement of vector-mediated immune control, manipulation of the insect microbiome, or use of powerful new genetic tools such as CRISPR-Cas systems to edit vector genomes. Finally, we offer a perspective on the implementation hurdles as well as the knowledge gaps that must be filled in the coming years to safely realize the potential of these novel strategies to eliminate the scourge of vector-borne disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Interactions between the Anopheles mosquito vector and Plasmodium parasites shape how malaria is transmitted in endemic regions. The long association of these two organisms has led to evolutionary ...processes that minimize fitness costs of infection and benefit both players through shared nutrient resources, parasite immune suppression, and mosquito tolerance to infection. In this review we explore recent data describing how Plasmodium falciparum, the deadliest malaria parasite, associates with one of its most important natural mosquito hosts, Anopheles gambiae, and we discuss the implications of these findings for parasite transmission and vector control strategies currently in development.
Parasites can exploit mosquito resources for their own development.Reproductive fitness costs are minimized in natural combinations of Plasmodium and Anopheles.A mating-induced tolerance mechanism has evolved in Anopheles gambiae to limit reproductive fitness costs of high-intensity Plasmodium infections.Nutrient resources within the mosquito can affect parasite development, sporozoite function, and infectivity.Manipulations to mosquito physiology have consequences for malaria transmission and proposed vector control strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Many mosquito species, including the major malaria vector Anopheles gambiae, naturally undergo multiple reproductive cycles of blood feeding, egg development and egg laying in their lifespan. Such ...complex mosquito behavior is regularly overlooked when mosquitoes are experimentally infected with malaria parasites, limiting our ability to accurately describe potential effects on transmission. Here, we examine how Plasmodium falciparum development and transmission potential is impacted when infected mosquitoes feed an additional time. We measured P. falciparum oocyst size and performed sporozoite time course analyses to determine the parasite's extrinsic incubation period (EIP), i.e. the time required by parasites to reach infectious sporozoite stages, in An. gambiae females blood fed either once or twice. An additional blood feed at 3 days post infection drastically accelerates oocyst growth rates, causing earlier sporozoite accumulation in the salivary glands, thereby shortening the EIP (reduction of 2.3 ± 0.4 days). Moreover, parasite growth is further accelerated in transgenic mosquitoes with reduced reproductive capacity, which mimic genetic modifications currently proposed in population suppression gene drives. We incorporate our shortened EIP values into a measure of transmission potential, the basic reproduction number R0, and find the average R0 is higher (range: 10.1%-12.1% increase) across sub-Saharan Africa than when using traditional EIP measurements. These data suggest that malaria elimination may be substantially more challenging and that younger mosquitoes or those with reduced reproductive ability may provide a larger contribution to infection than currently believed. Our findings have profound implications for current and future mosquito control interventions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, ...are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Understanding of human structural brain development has rapidly advanced in recent years, but remains fundamentally “localizational” in nature. Here, we use 376 longitudinally acquired structural ...brain scans from 108 typically developing adolescents to conduct the first study of coordinated anatomical change within the developing cortex. Correlation in rates of anatomical change was regionally heterogeneous, with fronto-temporal association cortices showing the strongest and most widespread maturational coupling with other cortical areas, and lower-order sensory cortices showing the least. Canonical cortical systems with rich structural and functional interconnectivity showed significantly elevated maturational coupling. Evidence for sexually dimorphic maturational coupling was found within a frontopolar-centered prefrontal system involved in complex decision-making. By providing the first link between cortical connectivity and the coordination of cortical development, we reveal a hitherto unseen property of healthy brain maturation, which may represent a target for neurodevelopmental disease processes, and a substrate for sexually dimorphic behavior in adolescence.
► Rates of structural maturation are highly coordinated within the cortical sheet ► Maturational coupling with other cortices is maximal in association cortex ► Maturational coupling echoes known patterns of structural and functional connectivity ► Prefrontal maturational coupling in adolescence is sexually dimorphic
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AbstractObjectiveTo derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. MethodsRespondents from the US adult ...population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. ResultsOf 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from −0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). ConclusionsA societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We sought to compare the diagnostic performance of coronary computed tomography angiography (CCTA), computed tomography perfusion (CTP), and computed tomography (CT)-fractional flow reserve (FFR) for ...assessing the functional significance of coronary stenosis as defined by invasive FFR in patients with known or suspected coronary artery disease (CAD). CCTA has proved clinically useful for excluding obstructive CAD because of its high sensitivity and negative predictive value (NPV); however, the ability of CTA to identify functionally significant CAD has remained challenging. We searched PubMed/Medline for studies evaluating CCTA, CTP, or CT-FFR for the noninvasive detection of obstructive CAD compared with catheter-derived FFR as the reference standard. Pooled sensitivity, specificity, PPV, NPV, likelihood ratios, and odds ratio of all diagnostic tests were assessed. Eighteen studies involving a total of 1,535 patients were included. CTA demonstrated a pooled sensitivity of 0.92, specificity 0.43, PPV of 0.56, and NPV of 0.87 on a per-patient level. CT-FFR and CTP increased the specificity to 0.72 and 0.77, respectively (p = 0.004 and p = 0.0009) resulting in higher point estimates for PPV 0.70 and 0.83, respectively. There was no improvement in the sensitivity. The CTP protocol involved more radiation (3.5 mSv CCTA vs 9.6 mSv CTP) and a higher volume of iodinated contrast (145 ml). In conclusion, CTP and CT-FFR improve the specificity of CCTA for detecting functionally significant stenosis as defined by invasive FFR on a per-patient level; both techniques could advance the ability to noninvasively detect the functional significance of coronary lesions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We demonstrate a novel response of a nonlinear micromechanical resonator when operated in a region of strong, nonlinear mode coupling. The system is excited with a single drive signal and its ...response is characterized by periodic amplitude modulations that occur at timescales based on system parameters. The periodic amplitude modulations of the resonator are a consequence of nonlinear mode coupling and are responsible for the emergence of a "frequency-comb" regime in the spectral response. By considering a generic model for a 1∶3 internal resonance, we demonstrate that the novel behavior results from a saddle node on an invariant circle (SNIC) bifurcation. The ability to control the operating parameters of the micromechanical structures reported here makes the simple micromechanical resonator an ideal test bed to study the dynamic response of SNIC behavior demonstrated in mechanical, optical, and biological systems.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
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